Rotating Catalysts Are Superior: Suppressing Product Inhibition by Anchimeric Assistance in Four-Component Catalytic Machinery

Three distinct four-component supramolecular nanorotors, prepared by varying the rotator’s structure and keeping all other components constant, exhibit rotational frequencies that differ by almost 2 orders of magnitude. When the rotors were used as catalyst for two click reactions, the product yield correlated with the speed of the machine, e.g., 20% at 0.50 kHz, 44% at 20 kHz and 62% at 42 kHz. The kinetic effect on the product yield is attributed to the ability of the rotating catalysts to displace the product more efficiently from the active site at higher speed (anchimeric assistance). This mechanistic hypothesis was convincingly corroborated by a linear correlation between product yield and product liberation

Thailandins A and B, New Polyene Macrolactone Compounds Isolated from Actinokineospora bangkokensis Strain 44EHW^T, Possessing Antifungal Activity against Anthracnose Fungi and Pathogenic Yeasts

Two new polyene macrolactone antibiotics, thailandins A, <b>1</b>, and B, <b>2</b>, were isolated from the fermentation broth of rhizosphere soil-associated Actinokineospora bangkokensis strain 44EHW^T. The new compounds from this strain were purified using semipreparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds demonstrated broad spectrum antifungal activity against fungi causing anthracnose disease (Colletotrichum gloeosporioides DoA d0762, Colletotrichum gloeosporiodes DoA c1060, and Colletotrichum capsici DoA c1511) as well as pathogenic yeasts (Candida albicans MT 2013/1, Candida parasilopsis DKMU 434, and Cryptococcus neoformans MT 2013/2) with minimum inhibitory concentrations ranging between 16 and 32 μg/mL. This is the first report of polyene antibiotics produced by Actinokineospora species as bioactive compounds against anthracnose fungi and pathogenic yeast strains

New Simocyclinones: Surprising Evolutionary and Biosynthetic Insights

Simocyclinone D8 (<b>1</b>, SD8) has attracted attention due to its highly complex hybrid structure and the unusual way it inhibits bacterial DNA gyrase by preventing DNA binding to the enzyme. Although a hypothesis explaining simocyclinone biosynthesis has been previously proposed, little was proven <i>in vivo</i> due to the genetic inaccessibility of the producer strain. Herein, we report discovery of three new D-type simocyclinones (D9, D10, and D11) produced by Kitasatospora sp. and Streptomyces sp. NRRL B-24484, as well as the identification and annotation of their biosynthetic gene clusters. Unexpectedly, the arrangement of the newly discovered biosynthetic gene clusters is starkly different from the previously published one, despite the nearly identical structures of D8 and D9 simocyclinones. The gene inactivation and expression studies have disproven the role of a modular polyketide synthase (PKS) system in the assembly of the linear dicarboxylic acid. Instead, the new stand-alone ketosynthase genes were shown to be involved in the biosynthesis of the tetraene chain. Additionally, we identified the gene responsible for the conversion of simocyclinone D9 (<b>2</b>, SD9) into D8